Neuroprotective role of Lactiplantibacillus plantarum C10-derived SCFAs: a functional food approach targeting gut-brain-axis disruption in rotenone-induced Parkinson's disease in-vivo in adult zebrafish.

INTRODUCTION: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal degeneration, oxidative stress, neuroinflammation, and gut microbiota dysbiosis. Increasing evidence highlights the role of the gut-brain axis (GBA) and probiotic-derived short-chain fatty acids (SCFAs) in modulating neuroinflammation and disease progression. This study investigated the neuroprotective potential of SCFAs produced by Lactiplantibacillus plantarum C10 in a rotenone-induced PD zebrafish model. METHODS: SCFA-producing lactic acid bacteria were isolated from traditionally fermented cabbage (sauerkraut), and the most promising isolate was identified as L. plantarum C10 using morphological, biochemical, phylogenetic, and 16S rRNA gene sequencing analyses. Fermentation conditions were optimized to maximize SCFA production, and the metabolites were characterized using Fourier-transform infrared spectroscopy (FTIR) and high-performance liquid chromatography (HPLC). Antioxidant activity was evaluated using DPPH and ABTS assays. Developmental toxicity was assessed in zebrafish embryos, followed by therapeutic evaluation in rotenone-induced adult zebrafish through behavioural, biochemical, molecular, and histopathological analyses. RESULTS: L. plantarum C10 exhibited strong probiotic characteristics, including antimicrobial activity, acid and bile tolerance, homofermentative metabolism, and extracellular polysaccharide production. Optimized fermentation significantly enhanced SCFA-associated metabolite production, while FTIR and HPLC confirmed the presence of fermentation-derived organic acid metabolites. The metabolites demonstrated potent antioxidant activity and showed minimal developmental toxicity up to 30 mg/mL in zebrafish embryos. In the rotenone-induced PD model, C10-derived SCFAs restored antioxidant enzyme activities, reduced oxidative stress, improved locomotor and cognitive performance, modulated genes associated with neuronal function, inflammation, the NRF2 signalling pathway, intestinal barrier integrity, and gut microbiota, and preserved normal brain and intestinal histoarchitecture. DISCUSSION: These findings demonstrate that L. plantarum C10-derived SCFA metabolites exert antioxidant, anti-inflammatory, and neuroprotective effects through modulation of the gut-brain axis. This study highlights the potential of probiotic-derived SCFAs as functional food-based therapeutic candidates for managing Parkinson's disease and associated gut dysbiosis.